Zhang Yikai, Zeng Chengwu, Lu Shuai, Qin Tianyu, Yang Lijian, Chen Shaohua, Chen Jie, Li Yangqiu
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China; First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China; First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
Biochem Biophys Res Commun. 2016 Sep 30;478(4):1758-63. doi: 10.1016/j.bbrc.2016.09.020. Epub 2016 Sep 6.
Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs. Moreover, we demonstrate that the expression of miR-125b targets is downregulated in leukemic cells in patients with APL. Thus, our results provide evidence that miR-125b can modulate multiple oncogenic cell proliferation pathways and may be a novel therapeutic target for APL.
急性早幼粒细胞白血病(APL)的特征是存在PML-RARα融合蛋白。我们之前发现,PML-RARα调控的miR-125b在APL中高表达;然而,miR-125b参与APL增殖的调控作用及机制的特点尚未阐明。在本研究中,我们证明miR-125b通过PI3K/Akt和MAPK信号通路促进APL细胞的增殖。此外,我们鉴定出BTG2、MAP3K11、RPS6KA1和PRDM1为miR-125b的假定靶标,并使用荧光素酶报告基因构建体进行了验证。此外,我们证明APL患者白血病细胞中miR-125b靶标的表达下调。因此,我们的结果提供了证据,表明miR-125b可调节多种致癌细胞增殖途径,可能是APL的一个新的治疗靶点。